Nuclear medicine and biology · 2021
Cell death PET/CT imaging of rat hepatic fibrosis with 18F-labeled small molecule tracer.
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Su Shu, Xiang Xianhong, Lin Liping, Xiong Ying, Ma Hui, Yuan Gongjun, Zhao Jing, Zhang Zhanwen, Liu Shaoyu, Nie Dahong, Tang Ganghua
Аннотация
PURPOSE: To evaluate the potential feasibility of Al[18F]F-1,4,7-triazacyclononane-1,4,7-triaceticacid (NOTA)-tripolyethylene glycol (PEG3)-Duramycin (Al[18F]F-NOTA-PEG3-Duramycin) positron emission tomography (PET) for imaging of rat hepatic fibrosis.
PROCEDURES: Hepatic fibrosis rat models were injected with thioacetamide (TAA), control rats received saline (n = 12 per group). Rats in the two groups underwent PET imaging using Al[18F]F-NOTA-PEG3-Duramycin and [18F]FDG at multiple time points (2, 4, 6, and 8 weeks after TAA or saline treatment). Between-group differences in the apoptosis rate, fibrotic activity, and liver uptake of Al[18F]F-NOTA-PEG3-Duramycin or [18F]FDG were assessed using Student's t-test. Imaging results were cross-validated using histopathology detection and Pearson's correlation test was used to assess the association relationships between radioactive uptake value and quantified histopathological data.
RESULTS: Compared with control group at multiple time points, each TAA group showed a higher radioactive liver uptake of Al[18F]F-NOTA-PEG3-Duramycin (each P < 0.05). Furthermore, the increase in the liver uptake of Al[18F]F-NOTA-PEG3-Duramycin was proportional to the progression of fibrosis (R2 = 0.8846, P < 0.001) and apoptosis rate (R2 = 0.9208, P < 0.001) in the TAA group. Meanwhile, there were also between-group differences in [18F]FDG uptake in each phase (P < 0.05), however, no relationship between [18F]FDG uptake and the fibrotic activity was observed.
CONCLUSIONS: Al[18F]F-NOTA-PEG3-Duramycin PET/CT could be applied to monitor the progression of liver fibrosis, whereas [18F]FDG PET/CT could not. Implications of this work for noninvasive diagnosis of liver fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.
PROCEDURES: Hepatic fibrosis rat models were injected with thioacetamide (TAA), control rats received saline (n = 12 per group). Rats in the two groups underwent PET imaging using Al[18F]F-NOTA-PEG3-Duramycin and [18F]FDG at multiple time points (2, 4, 6, and 8 weeks after TAA or saline treatment). Between-group differences in the apoptosis rate, fibrotic activity, and liver uptake of Al[18F]F-NOTA-PEG3-Duramycin or [18F]FDG were assessed using Student's t-test. Imaging results were cross-validated using histopathology detection and Pearson's correlation test was used to assess the association relationships between radioactive uptake value and quantified histopathological data.
RESULTS: Compared with control group at multiple time points, each TAA group showed a higher radioactive liver uptake of Al[18F]F-NOTA-PEG3-Duramycin (each P < 0.05). Furthermore, the increase in the liver uptake of Al[18F]F-NOTA-PEG3-Duramycin was proportional to the progression of fibrosis (R2 = 0.8846, P < 0.001) and apoptosis rate (R2 = 0.9208, P < 0.001) in the TAA group. Meanwhile, there were also between-group differences in [18F]FDG uptake in each phase (P < 0.05), however, no relationship between [18F]FDG uptake and the fibrotic activity was observed.
CONCLUSIONS: Al[18F]F-NOTA-PEG3-Duramycin PET/CT could be applied to monitor the progression of liver fibrosis, whereas [18F]FDG PET/CT could not. Implications of this work for noninvasive diagnosis of liver fibrosis, assessment of fibrotic activity, and evaluation of antifibrotic therapy are expected.